Hume was the son of the radical politician Joseph Hume. He entered the Indian civil service in Bengal in 1849. After serving as magistrate in the district of Etawah at the time of the Indian Mutiny of 1857–58, he was assigned to the board of revenue in the North-Western Provinces. In 1870–79 he worked for the central government of India as secretary in the revenue and agriculture department. His views favouring greater participation for Indians in governmental affairs created difficulties, and he returned to provincial administration. On his retirement from the civil service in 1882, he involved himself in political activities aimed at giving Indians a more democratic, representational government and was one of the conveners of the first session of the Indian National Congress, held at Bombay (Mumbai) in 1885. He served as general secretary of the Congress for its first 22 years.

By the time he left India in 1894, Hume was no longer able to control the nationalist movement, in which radical ideas were gaining force. Retiring to the Dulwich district of London, he participated in and financed radical political causes, serving as president of the Dulwich Liberal Association from 1894 until his death.

While in the North-Western Provinces, he produced several works on ornithology, including, as coauthor, The Game Birds of India, Burmah and Ceylon (1879–81). He later presented his collection of bird skins and eggs to the British Museum.